# Role of Primary Sensory Neuron CaMKII Signaling in Regulation of Pain

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $629,263

## Abstract

Summary/Abstract
Chronic pain is a major public health challenge that is inadequately addressed. While opioids afford acute relief,
their chronic use often leads to addiction and intolerable side-effects in patients. We and others have shown that
dorsal root ganglion (DRG) field stimulation blocks pain in patients and pre-clinical models, which provides an
opportunity to directly identify the underlying mechanisms of neuropathic pain, and hopefully to find novel non-
opioid approaches to reduce pain. One protein we have identified to be a valid target is the calcium/calmodulin
(Ca2+/CaM)-dependent protein kinase (CaMKII), a critical regulator of the analgesic effects of DRG stimulation.
CaMKII is able to orchestrate diverse cellular functions to match required changes in excitable cell activity.
Knowledge on the role of CaMKII in regulating peripheral nervous system and primary sensory neuron function
is limited. Prior studies examining its role in pain have consistently associated it with mechanisms generating
pain rather than analgesia, based on experiments exposing both the peripheral nervous system and the central
nervous system to pharmacological inhibitors of CaMKII signaling. In contrast, our promising initial findings ex-
amining CaMKII signaling specifically in peripheral sensory neurons, i.e., those with their cell bodies in the DRGs,
indicate that painful conditions induced in preclinical models are associated with deficient sensory neuron
CaMKII signaling. Selective inhibition of peripheral sensory neuron CaMKII at the level of the DRG produces
hyperalgesia, while amplification of sensory neuron CaMKII signaling by molecular or electrical neuromodulation
approaches produces potent analgesia. We have developed viral approaches highly suited for selectively tar-
geting CaMKII in primary sensory neurons, and are proposing the following Aims to test the hypothesis that
reduced activity of CaMKII in peripheral sensory neurons drives the maintenance of chronic pain, and increasing
activity of CaMKII in DRG will alleviate chronic pain. Specifically, Aim 1. Establish the role of peripheral sensory
neuron CaMKII activity in suppressing pain. Aim 2. Identify the anatomic site of action for sensory neuron CaMKII
analgesia. Aim 3. Determine molecular mechanisms of CaMKII inactivation in animal and cell models of pain.
Completion of the proposed project will generate new insights on how sensory neuron CaMKII regulates the
development of neuropathic and osteoarthritic pain, along with proof-of-concept foundations for developing novel
opioid-free treatments based on selective reversal of chronic pain-induced down-regulated CaMKII activity.

## Key facts

- **NIH application ID:** 11084193
- **Project number:** 7R01NS128410-02
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Andy Hudmon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $629,263
- **Award type:** 7
- **Project period:** 2024-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11084193

## Citation

> US National Institutes of Health, RePORTER application 11084193, Role of Primary Sensory Neuron CaMKII Signaling in Regulation of Pain (7R01NS128410-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11084193. Licensed CC0.

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